Background: Up to half of NGU cases have no known etiology and no published studies have used molecular methods to identify novel microbes or microbial communities associated with idiopathic NGU.
Methods: Urine specimens from 18 heterosexual men with negative nucleic acid amplification tests for Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum-2 underwent broad-range 16S rRNA gene PCR and pyrosequencing (Roche 454) to identify urethral bacteria. Cases of NGU (n=12) had urethral discharge or >=5 PMNs/HPF; controls (n=6) had no discharge and <5 PMNs/HPF. Sequence reads were classified using a phylogenetic placement tool, pplacer, and a curated urogenital reference set. Rank abundance plots of detected species were created for each subject and aggregated by NGU status. Log-transformed sequence reads of detected bacteria were compared between cases and controls using the Student’s t-test. Shannon-Weiner diversity indices were compared using the Mann-Whitney-Wilcoxon (MWW) test.
Results: The microbiota of cases was dominated by Lactobacillus iners and significantly less diverse than that of controls (median diversity index 1.145 vs. 2.229, MWW p=0.03). Peptoniphilus harei was significantly less abundant in cases than controls (log-transformed mean 16S rRNA gene copies 1.84 vs. 5.15, p=0.05). Streptococcus mitis/oralis (3.53 vs. 6.09 log gene copies, p=0.07) and Finegoldia magna (2.68 vs. 4.96 log gene copies, p=0.16) were also less abundant in men with NGU than in controls. In contrast, L. iners was more abundant in cases than controls, although not statistically significant (7.24 vs. 6.22, p=0.36).
Conclusions: Surges in abundance of L. iners and decreased diversity of bacterial species in the urethral microbiota were associated with idiopathic urethritis. Many bacteria detected in these heterosexual men are frequently found in the vaginal microbiota, suggesting they are shared with or acquired from their female sex partners. Longitudinal studies are warranted to investigate the temporal relationships between bacterial acquisition and NGU.